title: Radiolabeling human peripheral blood stem cells for positron emission tomography (PET) imaging in young rhesus monkeys.
abstract: These studies focused on a new radiolabeling technique with copper ((64)Cu) and zirconium ((89)Zr) for positron emission tomography (PET) imaging using a CD45 antibody. Synthesis of (64)Cu-CD45 and (89)Zr-CD45 immunoconjugates was performed and the evaluation of the potential toxicity of radiolabeling human peripheral blood stem cells (hPBSC) was assessed in vitro (viability, population doubling times, colony forming units). hPBSC viability was maintained as the dose of (64)Cu-TETA-CD45 increased from 0 (92%) to 160 µCi/mL (76%, p>0.05). Radiolabeling efficiency was not significantly increased with concentrations of (64)Cu-TETA-CD45 >20 µCi/mL (p>0.50). Toxicity affecting both growth and colony formation was observed with hPBSC radiolabeled with ≥40 µCi/mL (p<0.05). For (89)Zr, there were no significant differences in viability (p>0.05), and a trend towards increased radiolabeling efficiency was noted as the dose of (89)Zr-Df-CD45 increased, with a greater level of radiolabeling with 160 µCi/mL compared to 0-40 µCi/mL (p<0.05). A greater than 2,000 fold-increase in the level of (89)Zr-Df-CD45 labeling efficiency was observed when compared to (64)Cu-TETA-CD45. Similar to (64)Cu-TETA-CD45, toxicity was noted when hPBSC were radiolabeled with ≥40 µCi/mL (p<0.05) (growth, colony formation). Taken together, 20 µCi/mL resulted in the highest level of radiolabeling efficiency without altering cell function. Young rhesus monkeys that had been transplanted prenatally with 25×10(6) hPBSC expressing firefly luciferase were assessed with bioluminescence imaging (BLI), then 0.3 mCi of (89)Zr-Df-CD45, which showed the best radiolabeling efficiency, was injected intravenously for PET imaging. Results suggest that (89)Zr-Df-CD45 was able to identify engrafted hPBSC in the same locations identified by BLI, although the background was high.
authors.affiliation: Department of Pediatrics, University of California Davis, Davis, California, United States of America ; Department of Cell Biology and Human Anatomy, University of California Davis, Davis, California, United States of America ; California National Primate Research Center, University of California Davis, Davis, California, United States of America.
authors.forename: Alice F
authors.initials: AF
authors.lastname: Tarantal
authors.forename: C Chang I
authors.initials: CC
authors.lastname: Lee
authors.forename: David L
authors.initials: DL
authors.lastname: Kukis
authors.forename: Simon R
authors.initials: SR
authors.lastname: Cherry
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000737:chemistry; D005260:Female; D006571:Heterocyclic Compounds / Q000008:administration & dosage; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage / Q000737:chemistry*; D007275:Injections, Intravenous; D017493:Leukocyte Common Antigens / Q000737:chemistry; D008253:Macaca mulatta; D008297:Male; D009942:Organometallic Compounds / Q000008:administration & dosage; D036102:Peripheral Blood Stem Cell Transplantation; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000494:pharmacology; D013194:Staining and Labeling / Q000379:methods*; D013234:Stem Cells / Q000737:chemistry* / Q000166:cytology; D015040:Zirconium / Q000737:chemistry
chemical_list: D000906:Antibodies; D006571:Heterocyclic Compounds; D018796:Immunoconjugates; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; C113624:copper(II)-1,4,8,11-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid; D003300:Copper; D015040:Zirconium; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human